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| Title | Structural basis for human chondroitin sulfate chain polymerization. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 16, Issue 1, Page 11663, Year 2025 |
| Publish date | Nov 26, 2025 |
Authors | Poushalee Dutta / Rosa L Cordeiro / Mélanie Friedel-Arboleas / Marie Bourgeais / Sylvain D Vallet / Margot Weber / Margaux Molinas / Huazhang Shu / Magnus N N Grønset / Rebecca L Miller / Elisabetta Boeri Erba / Rebekka Wild / ![]() |
| PubMed Abstract | Chondroitin sulfates are complex polysaccharide chains that regulate various biological processes at the cell surface and within the extracellular matrix. Here, we identify four heterodimeric ...Chondroitin sulfates are complex polysaccharide chains that regulate various biological processes at the cell surface and within the extracellular matrix. Here, we identify four heterodimeric complexes responsible for chondroitin sulfate chain polymerization in humans: CHSY1-CHPF, CHSY1-CHPF2, CHSY3-CHPF, and CHSY3-CHPF2. Using a custom-tailored in vitro glycosylation assay based on chemo-enzymatically synthesized fluorescent substrates, we demonstrate that all four complexes exhibit chain polymerization activity. The cryo-EM structure of the CHSY3-CHPF complex provides molecular insights into the chondroitin sulfate chain polymerization reaction. The architecture of the catalytic sites suggests that CHSY1 and CHSY3 are enzymatically active, while CHPF and CHPF2 primarily play a stabilizing role. Mutational analysis of purified enzyme complexes, combined with an in cellulo complementation assay, confirms that only CHSY1 and CHSY3 have bifunctional glycosyltransferase activities. Based on the spatial arrangement of the catalytic sites, we propose that chondroitin sulfate chain polymerization follows a non-processive, distributive mechanism. |
External links | Nat Commun / PubMed:41298522 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.9 - 3.0 Å |
| Structure data | EMDB-52913, PDB-9q8z: ![]() EMDB-53011: Focused refinement map of CHSY3-CHPF complex: N-terminal part ![]() EMDB-53012: Focused refinement map of CHSY3-CHPF complex: C-terminal part ![]() EMDB-53018: Consensus map of CHSY3-CHPF complex |
| Chemicals | ![]() ChemComp-NAG: ![]() ChemComp-UDP: ![]() ChemComp-MN: |
| Source |
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Keywords | TRANSFERASE / glycosyltransferase / chondroitin sulfate / polymerization / heterodimeric complex |
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homo sapiens (human)
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